A DOUBLE-MASKED COMPARISON OF NAPRELAN(R) AND NABUMETONE IN OSTEOARTHRITIS OF THE KNEE

The efficacy and safety of Naprelan(R) (naproxen sodium) 1000 mg once daily (QD) and nabumetone 1500 mg QD were compared in a multicenter, r andomized, parallel-group, placebo-controlled, double-masked, 4-week s tudy of adult outpatients with active osteoarthritis (OA) of the knee. Nabumetone 1500 mg was chosen for comparison because it is commonly p rescribed in a QD dosing regimen for OA. After a washout period free o f nonsteroidal anti-inflammatory drugs, 279 patients were enrolled and assigned randomly to treatment with either Naprelan 1000 mg QD (n = 9 2), nabumetone 1500 mg QD (n = 93), or placebo (n = 94). All treatment s were evaluated for efficacy and safety at baseline and at weeks 2 an d 4 of the treatment period or at discontinuation. Demographic charact eristics were comparable among all treatment groups. As might be expec ted in a study of OA of the knee, a majority of patients enrolled were women (68.8%), and many were obese (mean weight, 195.6 Ib; mean heigh t, 66 in). Significantly fewer patients (13) treated with Naprelan pre maturely discontinued the study than did patients treated with placebo (27); there was a lower rate of discontinuation for insufficient ther apeutic effect in the Naprelan group compared with the nabumetone and placebo groups. Using an intent-to-treat model, the overall distributi on of scores in all three primary efficacy assessments (investigator's global assessment of OA, patient's global assessment of OA, and walki ng pain) at week 2 and at the last visit was significantly better for the Naprelan group compared with both the nabumetone and placebo group s. The mean improvement from baseline was also significant for Naprela n compared with the nabumetone and placebo groups for all three assess ments at week 2 and for investigator's global assessment of OA and wal king pain at the last visit. The nabumetone-treated group showed signi ficant improvement over the placebo-treated group in only one primary assessment: mean change from baseline in patient's global assessment o f OA at week 2. At week 2, significant differences favoring Naprelan v ersus nabumetone and placebo were measured in overall distribution of scores for joint tenderness and nighttime pain. Distribution of qualit y of sleep and inactivity stiffness scores also improved relative to p lacebo at week 2. At the last visit, nighttime pain scores were still significantly better for patients receiving Naprelan versus nabumetone and placebo. Patients receiving nabumetone had statistically signific ant improvement from baseline in inactivity stiffness compared with pl acebo at week 2. There were no clinically important differences among treatment groups in the occurrence of adverse events or laboratory abn ormalities. The results of this 4-week study of Naprelan 1000 mg QD co mpared with nabumetone 1500 mg QD demonstrate at least equal efficacy (superior efficacy was demonstrated for several parameters) and equal safety in adult outpatients with active OA of the knee.